Exploiting the Biginelli reaction: nitrogen-rich pyrimidine-based tercyclic α-helix mimetics
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- 作者：Zelong Lim<sup>asup><sup> ; sup><sup>bsup> ; Peter J. Duggan<sup>bsup><sup> ; sup><sup>csup> ; Soo San Wan<sup>dsup><sup> ; sup><sup>esup> ; Guillaume Lessene<sup>dsup><sup> ; sup><sup>esup><sup> ; sup><sup>fsup> ; Adam G. Meyer<sup>bsup><sup> ; sup><sup>Adam.Meyer@csiro.au" class="auth_mail" title="E-mail the corresponding authorsup> ; Kellie L. Tuck<sup>asup><sup> ; sup><sup>Kellie.Tuck@monash.edu" class="auth_mail" title="E-mail the corresponding authorsup>
- 关键词：Biginelli reaction ; Pyrimidine ; Alpha-helix mimetics ; Bcl-xL inhibitor
- 刊名：Tetrahedron
- 出版年：2016
- 出版时间：3 March 2016
- 年：2016
- 卷：72
- 期：9
- 页码：1151-1160
- 全文大小：810 K
文摘
Several rationally designed pyrimidine-based scaffolds intended to mimic the spatial projection of the i, i+3, and i+7 residues of an α-helix and also possess improved aqueous solubility were prepared. A Biginelli-oxidation process was used to form the central pyrimidine ring of these scaffolds, which was subsequently manipulated to form pyrimidine-based tercyclic α-helix mimetics. A pyrimidine-based scaffold designed to mimic the α-helical BH3 domain of the pro-apoptotic Bak protein was also prepared as a putative inhibitor of the Bcl-x<sub>Lsub>/Bak protein-protein interaction. The pyrimidine-based tercyclic α-helix mimetics, and the putative Bcl-x<sub>Lsub> inhibitor, were assessed using a luminescence competition assay, however, none displayed inhibitory activity against Bcl-x<sub>Lsub> or Mcl-1.